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Monthly Archives: May 2013

A point mutation in a gene leads to a phenomenal effect on the phenotype. It is a classic Biochemistry textbook case study, Sickle Cell Anemia. The mutant hemoglobin has a Valine instead of the Glutamic acid. The change is highly observable in the form of a debilitating condition. But, not all point mutations in the protein sequence are debilitating, and sometimes they give rise to something spectacular. One such example is the White Tiger, frequently mistaken as an albino. The recent publication in Current Biology [1] has been picked up by many newspapers and is creating news. See here, here, and here. There are two reasons as to why this research has become news. For one, it is about the endangered species and Tiger conservation. Second, it is precisely pinpointing to a molecular level change that can now be understood.

In sickle cell anemia, the longer and charged Glutamic acid changes to a uncharged Valine, thereby wrecking havoc.

Screen Shot 2013-05-24 at 12.14.27 PMResearchBlogging.orgThe gene in limelight is SLC45A2, which is present in many vertebrates including Humans. (Uniprot id: Q9UMX9) In humans this “pigmentation related gene in humans, whose polymorphisms are associated with light skin color in modern Europeans and pathogenic mutations known to cause oculocutaneous albinism type 4“. From a structural bioinformatics perspective, the paper provides as to how this mutation can be understood towards its function in the mutant. It is a membrane protein and the solved structure is not available, but the homology modeled structure is available in ModBase [2]. See below the modeled protein structure from ModBase, with the position 477 highlighted. Figure 3 of the paper shows a different way of showing the multiple sequence alignment.

Human SLC45A2 highlighting the Alanine 477

Human SLC45A2 highlighting the Alanine 477

13694324975636

The residue 477 (Alanine is conserved among many vertebrates) is in the 11th transmembrane helix, and the change from Alanine to Valine, is possibly thought to prevent melanin synthesis therefore the while tiger! In the case of Sickle cell Anemia, one theory is that the mutation could have some evolutionary pressure, that is due to high prevalence of malaria. It so happens that people suffering from sickle cell anemia, do not get malaria, they are resistant to it.

In Tigers, the orange coloration of the fur, helps it to camouflage among the grasslands and forests. But, in the case of white tiger, what could have been the evolutionary pressure? This question remains in my mind after reading this paper.

References

  1. Xu, X., Dong, G., Hu, X., Miao, L., Zhang, X., Zhang, D., Yang, H., Zhang, T., Zou, Z., Zhang, T., Zhuang, Y., Bhak, J., Cho, Y., Dai, W., Jiang, T., Xie, C., Li, R., & Luo, S. (2013). The Genetic Basis of White Tigers Current Biology DOI: 10.1016/j.cub.2013.04.054
  2. http://modbase.compbio.ucsf.edu/modbase-cgi/model_details.cgi?queryfile=1369410401_8612&searchmode=default&displaymode=moddetail&referer=yes&snpflag=&
  3. http://www.uniprot.org/uniprot/Q9UMX9
  4. http://en.wikipedia.org/wiki/SLC45A2
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What would be like to teach a class or describe someone about a protein, without visualizing its structure? Boring is one word that pops in my mind. I vividly remember the professor drawing two blobs touching each other, to describe protein-protein interaction, while explaining it either on the blackboard or on the transparencies of a over-head projector. Those were the days! Tracing back nearly 60 years back, when John Kendrew showed everyone a coiled mess, it has fueled every scientist’s imagination to visualize a protein. The coiled mess is aptly titled “Turd of the century”!

Myoglobin 1

Image Courtesy: Stephen Curry, Flickr.
Image reproduced under Creative Common Licence

If you are in UK, Click here to see the exhibit of myoglobin, and the accompanying Guardian article. If John Kendrew had the plethora of visualization choices like we have today, what could have happened?

Coming to today, it is become so routine to use a molecular visualization tool to check-out a protein. And most journals contain the Jmol plugin while browsing the full text of any article, if they discuss any structures from the PDB. So, when a survey was recently conducted by Craig P. A. et al to estimate the effectiveness of these tools, certain things were obvious.

  • Molecular visualization software/tools is akin to Oxygen for researchers and most importantly, for educators.
  • They make it fun to understand the complex biology behind every structure

It makes sense to survey only about freeware since

neither student nor faculty are usually willing (or able) to pay for commercial molecular visualization software when freeware applications are available

ResearchBlogging.org10 years ago, I used to use Chime very frequently and now Jmol has replaced it as the web plugin. (Whatever happened to Chime?) The majority of people who participated in the survey were associate professors, using Windows and have been using the various tools for the past 5-10 years. The biggest use was for teaching biochemistry classes. It is no surprise that PyMOL came across as the most frequently used software. However, the supported version being commercially sold by Schrodinger, many participants from small undergrad institutions have voiced their dissatisfaction about it. Since, the educational version is a pain.

The survey posted some interesting open-ended questions:

  1. What additional resources would you like to have available to teach molecular structures?
  2. What would you like to be able to do with 3D molecular visualization programs that you currently cannot do?

For the second, question many wanted “a simple way to create animations/morphs between structures”. The authors noted that while there are resources available inherently with the tool the participants were using. There was a clear lack of awareness of the full-potential of the software they were using. Readers of this blog would remember the previous post of making animated gifs of proteins (Yes, it is pronounced as Jif!).  Also, the Yale Morph Server does a good job of showing conformational change in a protein.

To tackle this issue, some universities have a one-semester course for graduate students and postdocs, where they teach how to use visualization tools and also how to best present a molecular structures. But, for others who don’t have such courses scroll down to the end to see some practical solutions.

How does the future look like?

From the survey, it looked like four areas needed more concentration

  • Assessment – How to know exactly if the student understood the background of the protein? In other words, some type of rubric to follow. Rubrics might be easier for assessing undergrad classes in an uniform way, but make it complex for assessing the graduate student who is working on a narrow-down topic
  • Support – Need for tutorials for users at different levels
  • Attitude – That is there exists a kind of wall between the student and the computer.
  • Software – Can ONE software do everything that VMD, Chimera, and PyMOL put together? I really like that idea!

Among the wishlist the participants asked was to have the tool efficiently demonstrate dynamics, motions, protein-ligand interactions. To some extent, depending on which tool one is using, these are implemented as plugins or modules. This brings us back to the topic of creating awareness about the tool in use.

How to create your own custom tutorial to learn a new molecular visualization tool?

So, you have come across a new freeware, mentioned by your colleague or read somewhere, and want to use it. Some tips that would be useful are as follows:

  1. If you don’t have permissions to install, of course you need to get your administrator to install it. There is always the alternative of installing it in your laptop. If you are really apprehensive about the tool, create a guest account (with no administrative permissions) and install it in the desktop area.
  2. Almost all tools come with tutorials as to how to take the baby-steps of learning the tool.  If you don’t like it, download a PDB file from this link. It has PDB entries with “Only Protein with Ligand”
  3. As a kid if you have broken down a new toy to its nuts and bolts and recreated it back to factory settings, then this step is easier. Basically, try every option one after another. This might take time and can be somewhat frustrating. But, there are “Aah” moments while doing it and the time invested now is greatly rewarding when you have to figure out with your protein of interest.
  4. Google “The tool in use” and search in images, you will see a plethora of images made by others which can be taken as a small assignment to take up. Don’t worry about completing it to the end. The objective is to  getting to know the software/tool rather than getting good results
  5. If you like the tool, try recreating something interesting that you had done with another tool. Compare and contrast. Now, you know something that others don’t!

References:

  1. Craig, P., Michel, L., & Bateman, R. (2013). A survey of educational uses of molecular visualization freeware Biochemistry and Molecular Biology Education, 41 (3), 193-205 DOI: 10.1002/bmb.20693
  2. http://www.guardian.co.uk/science/occams-corner/2013/apr/19/1
  3. http://www.sciencemuseum.org.uk/visitmuseum/galleries/crystallography.aspx
  4. http://molmovdb.mbb.yale.edu/molmovdb/morph/

Are you looking for opportunity to hone your writing skills? And at the same time get recognition for doing that? Look no further than the Wiki Contest from Biophysical Society.

http://www.biophysics.org/AwardsOpportunities/SocietyContests/WikiEditingContest/tabid/4125/Default.aspx

http://biophysicalsociety.wordpress.com/2013/02/21/improve-biophysics-information-on-wikipedia-and-enter-to-win/

Share what you know about biophysics with the world by participating in the Society’s Wiki-Edit Contest! The 2013 contest kicked off at the 57th Annual Meeting, and attendees at the kick off event received a button with the image on the left.

Six winners, chosen by a panel of judges who will determine the most improved biophysics-related articles, image collections or other contributions to Wikipedia or Commons, will receive $100 each, a barnstar on their talk page, and free registration to the 2014 Annual Meeting in San Francisco, California.

Visit the WikiProject Biophysics page for more information about the WikiProject. Visit the Biophysics Wiki-Edit Contest page or search WP:BIOPHYS on Wikipedia or Google for information on how to enter the contest.

For helpful tips and tricks for creating a Wikipedia account, adding and editing pages, and more, view the slides presented at the BPS Annual Meeting Wiki-Editing Contest Meet-Up!

The deadline to finish your article is July 15, 2013.

It is refreshing to see, literally, someone dancing as a protein! And when it is choreographed well, it becomes a awesome video to show in your class.

Recently, Biophysical Society had launched the “Biophysics—The Everyday” video contest “that explained how biophysics affected everyday life”. The following video, explaining protein folding, was picked as a winner. Congrats to the winner!

Seeing the protein folding dance, I remembered this vintage Protein synthesis dance, I had seen long time back. Enjoy your Friday!

In this age, where many readers have a breath-wise/skimming habit of reading things, instead of depth-wise [Ref 1, 2], blogs are an awesome since you can write as much as you want, post as many pictures one wants to. Blogging by those who are in science is a one of the ways of bridging the gap of communication that is abysmally low between researchers and the non-scientific public. No, not as a propaganda machine, but reaching out to the people who are interested in what one is talking about.

PLoS Biology’s article “An Introduction to Social Media to Scientists” sets the right pitch for those who are thinking of whether they should take the plunge to blogging or not! Read the article here [Ref 3]

Of course, there are other ways of communicating in the social media. But, I will for time being stick to blogs for the two main reasons mentioned by Birk and Goldstein

Longevity; posts are accesible via search engines

Robust platform for building an online reputation.

ResearchBlogging.org

One other effective way of making an online reputation is by editing Wikipedia articles. As of now, I find blogging about research articles to be highly rewarding for the following reasons

  • Sharpening my writing skills (I don’t have to emphasize the importance of this skill for researchers whose native language is not English)
  • Expressing one’s views in a professional manner
  • Making me find more interesting articles that I can blog about, which translates to more reading done as well.
  • For every post, I see my brain working the process of forming an idea, and finally seeing the effort achieve fruition. (This is very helpful to plan the way your write your manuscript with your own results)
  • A sense of satisfaction that comes after clicking the button “Publish”

Read here more about Research blogging!

References

  1. Literacy Debate: Online, R U Really Reading?
  2. What is the Internet’s Effect on Deep Reading?
  3. Bik HM, & Goldstein MC (2013). An introduction to social media for scientists. PLoS biology, 11 (4) PMID: 23630451